Stroke is the third leading cause of death and the leading cause of disability among adults. Recent studies have highlighted the importance of genetic factors in the etiology of several types of stroke. In particular, genetic epidemiologic and molecular genetic studies support the importance of genetic factors in the pathogenesis of familial intracranial aneurysms (IAs) and subarachnoid hemorrhage (SAH). The overall goal of this patient-oriented project is to advance the study of genetic factors responsible for familial IAs and SAH. The primary hypothesis is that specific mutations or susceptibility loci contribute to the development of familial IAs and SAH. Due to the paucity of families with multiple living affecteds having IAs or SAH, a candidate gene approach will be utilized initially. We will focus on genes involved in the metabolism of elastin, based on its importance in vascular integrity and prior studies showing altered elastin, elastase, and elastase inhibitors in patients with IAs and SAH. When adequate family resources are ascertained, genetic linkage studies will be performed. The identification of mutations or genetic susceptibility loci for familial IA/SAH will greatly influence the care of such patients as well as aid the screening and treatment of at-risk asymptomatic family members. This project has a major focus on patient-oriented research. The principal investigator will be involved in the diagnosis and ascertainment of families with IA/SAH. Asymptomatic at-risk family members will be counseled about the need to undergo screening for unruptured IAs using non-invasive techniques such as magnetic resonance angiography and CT angiography. The laboratory based research will focus on screening candidate genes using PCR, SSCP and DNA sequencing techniques. This research project combined with the PI's background and expertise provide a wide range of patient-oriented mentorship opportunities in clinical and genetic research.